Process for the preparation of myosmine



' Patented Aug. 7, 1945 v 2,381,328" I I H i M PROCESS FOR THE PREPARATION OF g 'MYOSMINE r I; f Charles F. Woodward, Abin'gtoniandlAbner Eisner and Paul G. Haines, Philadelphia Pa, assignfors v to the United States of America as represented by Claude R. Wickard, Secretary of Agriculture, and his successors in oflice I K d No Drawing. Application October 19 4 3,: in 4 Serial NO; 507,892 1 e .4 Claims." ('01. zoo-236b V (Granted underjthe act of March-3.11883};as.

Y amended fil Q iO l is S madeunder the act I of March 3, 1883, as amended by the act of; April 3 9 andthe invention herein described, if

patented, may h manufactured' and used: by or {or} cgovermnent of the United Statesoi Amer 1ca for. governmental purposes without the ,pay,-,

merit tons of anyroyalty thereon.

Our invention relates to the preparation of myosmine. Myosminehas been previously isolated in minute quantities; from tobacco smoke. Subsequent study'.-pf ,-thealkaloid obtained from this source led'to a determination of the approximate structural formula'of myosmine. act chemical structure was later postulated on April so, 192 370%0. G.,r5 1) following table ncliides the boiling points of myo'smine" fraction's collected at various reduced pressures? The ex- Pressure, mm.

B. P. range, C. 7

The above fractions readily solidified on cooling to about 5 C. and could be .further purified .the basis of a synthetic procedure in Which e yl by washing with chilled petroleum ether. A sam- 11190191118179 was condensed with N-benzoyl pyrroliple of myosmine subjected to this procedure meltdone and'the resulting product converted to myed t 443 4,5,0 Q, which agrees it th .osrnine' by hydrolysis with fuming hydrochloric ported melting point The carbon; hydrogen, acld under pressure- Y and nitrogen analytical values of this purified We ve ou d atyos ne ca be p epare product were in accord'with the theoretical comby the p oly of n e t temperatures bposition C9H10N2. The picric acid derivative of stantially above th rmal ilin p int of th the'alkaloid melted at 184.0 to 185.0 0., which is nicotine. This novel procedure facilitates the th reported melting of myosmine picrate, preparation of myosmine in quantities heretofore f 11owing examples i1lust t our invenunattainable since it is readily adaptable to large ti n; scale production. In view of the fact that this Example I alkaloid is reported to be responsible, wholly or in part, for the aroma of tobacco smoke, it is 220 grams of nicotine were passed over 124 cc. .possible that myosmine may prove avaluable adof 4-mesh quartz chips in an iron reactor at a junct to tobacco. In a copending application uniform rate over a period of 325 minutes. The filed concurrently herewith, we have shown that reactor consisted of an iron pipe of linch intersmall quantities of thisalkaloid impart a'characnal diameter which was supported in avertical, teristic aromatic flavor to tobacco and tobacco tubular, electrically heated furnace. The temsmoke. perature of the quartz chips was maintained at p In our process myosmine is obtained by passabout 550C. throughout the experiment. The ing nicotine over siliceous materials, such as silica pyrolysis P odu ts w e Collected in a re eiv n gel or fused quartz, at temperatures above 450 train consisting in turn of an ice-cooled flask, a C. The best yields of the desired product were water-cooled condenser, and a Dry-Ice trap, obtained at about 570 C. but pyrolyses conducted Distillation of the condensate through an efthroughout the temperature range 015% to 650 40 ficient fractipnating column yielded a fraction C. have produced myosmine. Space velocity varboiling at lr5.0 to 120C. at 3.4 mm. which solldiations between 136 and 332 have been successd on cooling to 5 C. The picric acid derivfully employed. The term space velocity, as ative of this material melted at about 184.0 to used herein, means the cc. of nicotine per hour 1 -O Whi h i the el in p int f myos in at reaction temperature per cc. of contact matepicrate. A sample of the white solid obtained rial. 130th Pyrex and iron have been found to by cooling the distilled fraction waswashed with be suitable reactor materials, chilled petroleum ether and dried on a porous Myosmine was isolated from the pyrolysisprodplate. The product melted at 44.0 to 45.0 C. ucts by distillation at sub-atmospheric pressures which is the reported melting point of myosmine. through an efilcient fractionating column. The Analysis: calculated for C9H10N22 C=73.97%,

H=6.85%, N 19.18%. Found: C=73.74%, H: 6.87%, N==19.38%. The identity of the myosmine was thereby confirmed.

Example I I 218 grams of nicotine were passed over 124 cc..

of 4-mesh quartz chips in the iron reactor described ingExar'nple' I; "'The addition" was made 1 at a uniform rate over a period of"190 minutes and the reaction temperature was maintained at,

about 650 C. Myosmine was isolated from the pyrolysis products according to the ,procedure disclosed in Example I. A picric acid derivative of l the myosmine fraction caused no melting point depression when mixed with the picric'acidvderivative obtained in the above example,

Example III The apparatus and volume of quartz contact material were identical with tha't employedin" Example I.

tained in Example I by the method of mixed melting points.

1 Example IV 201 grams of nicotine were passed over 168 cc.

' of 4-mesh quartz in a Pyrex reactor at a uniform rate over a period of 220 minutes. The reactor, which consisted of a Pyrex tube having anin ternal diameter of 1 inch, was supported in aivertical, tubular, electrically heated furnace. The

214 grams of nicotine were passed through the reactor at a uniform rate over a t temperature of the contact material in this experiment varied from 585 to 620 C. Myosmine was isolated and identified according to the procedure described in Example II.

Example V The quartz contact material employed in Example IV was replaced by-an equal ,volume of 4 to 6 meshsilica gel. 200 grams of nicotine were passed through the reactor at a uniform rate over a period of 200 minutes. The reaction temperature was 500 C. Myosmine was isolated and identified in the reaction products according to p the procedure disclosed in Example II.

- Having thusdescribed our invention, we claim:

' 1. The process of preparing myosmine which comprises pyrolyzing substantially pure nicotine in' the presence of' quartz at a temperature of about 500 to 650 C.

2; The process of preparing myosmine which comprises pyrolyzing substantially pure nicotine inthe presence of quartz at a temperature of about 570? C;

3-. The process of preparing myosmine which comprises pyrolyzing substantially pure nicotine in thepresence of silica gel at a temperature of about 500 0. p v p 4. Ina process of preparing myosmine the step comprising pyrolyzing substantially pure nicotine in the presence of a'contact material 'of' the group consistingofquartz and smeagel' at a temperature of about 500 to 650 C.

CHARLES F. WOODWARD'. ABNER EISNER. PAUL G. HATNES. 

